Specific autoantibodies of SLE, such as anti-Ku, anti-ribosome Po and anti-membrane DNA autoantibodies, in a case of human African trypanosomiasis.
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Biomedical subjects
Publications and source records attributed to G Servais.
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Despite health reform and increasing public investment in the health sector, utilization of curative health services, immunization coverage and patient satisfaction with the public health care system are steadily decreasing in Burkina Faso. It seems that the health care system itself is "ill". This paper examines the major symptoms associated with this illness. The central thesis suggests that any further improvement of health care performance in Burkina Faso will be subject to profound central reform in the area of human resources and financial management of the sector. Such a broad reform package cannot be achieved through the current project approach, but a sector-wide approach (SWAp) does not seem to be realistic at the present time. Policy discussions at a level higher than the Ministry of Health could be beneficial for achieving better donor coordination and increasing the commitment of the Ministry of Health to a sector-wide approach. Health sector reform issues and priorities and the role of international cooperation are reviewed and discussed.
The aim of this study is to evaluate, from 369 routine sera of SLE and control patients, the worth of anti double stranded nuclear DNA, anti nucleosomes autoantibodies and anti membrane DNA for the diagnosis of SLE. Cell membrane associated DNA (mDNA) has been described on B lymphocytes and monocytes, but not on T cells. Antibodies to mDNA were identified by an indirect immunofluorescence assay using a B cell line fixed but not permeabilised. At a 1:40 serum dilution, anti mDNA is almost associated with the diagnosis of systemic lupus erythematosus (SLE). Anti mDNA were shown to be different in specificity as compared with anti double stranded nuclear DNA. We compare its characteristics as diagnostic procedure to the conventional anti dsDNA antibody detection and to the recently introduced anti nucleosome antibody test documented as associated with SLE. It appears that the best sensitivity (0.65) and specificity (0.98) is given by the anti mDNA test.
OBJECTIVE: Autoantibodies to cell membrane associated DNA are described in systemic lupus erythematosus (SLE). The specificity of these antibodies differ from antibodies to nuclear DNA. METHODS: Using indirect immunofluorescence, a specific IgG was detected giving a characteristic pattern of continuous peripheral membrane fluorescence on cultured B-lymphocytes. RESULTS: This pattern was observed in 53 of 80 serum samples of SLE patients but absent in the serum samples of the control populations: 15 rheumatoid arthritis, 38 ankylosing spondylarthritis, 17 non-inflammatory osteopenic patients, and 224 blood donors. In 34 Sjögren syndrome's patients one only showed a positive test. The cmDNA specificity of these antibodies was confirmed by pattern extinction with DNAse but not RNase or protease pre-treatment of the cells. IgG to cmDNA, separated by absorption/elution from purified cmDNA immobilised on DEAE-nitrocellulose reproduced the immunofluorescence pattern pictures. Extensive serum depletion of anti-double strand or single strand DNA antibodies by absorption to cellulose bound ds- or ss-DNA affected marginally the pericellular fluorescence revealing some minor cross reactivity with nuclear DNA. Moreover, in SLE patients without detectable antibody to ds-DNA, pericellular fluorescence could be visible. CONCLUSION: This novel rapid immunofluorescence method may serve as an identification test of SLE patients. Given its positive (97.1%) and negative (92.9%) predictive value, sensitivity (66%) and specificity (99.5%), it improves on other diagnostic tests such as the detection of antibodies to Sm.
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BACKGROUND: This study is a continuation of a recent study, in which a defect in the immunoglobulin G (IgG) response to some natural antigens (bovine betalactoglobulin [BLG] from cow's milk and antigen p1 from the house dust mite Dermatophagoïdes pteronyssinus), usually presented at the mucosal level, was documented in lung cancer patients. The present study further characterizes this difference in terms of antibody relative functional affinity in the BLG model. METHODS: Relative functional affinity was evaluated by solid-phase enzyme-linked immunosorbent assay in terms of the relationship between specific IgG retention, assessed with peroxidase-labeled protein A, and serial dilutions of IgG fractions isolated from 24 sera from lung cancer patients and 24 sera from healthy control subjects matched for their anti-BLG IgG antibody titers. The procedure was performed in the presence and absence of low concentrations of diethylamine, which was expected to prevent low-affinity antigen-antibody binding without affecting the binding of high-affinity antibodies. Anti-BLG IgG antibody affinity also was evaluated in 25 patients with early-stage lung cancer, before and after (5 +/- 1 week) complete surgical excision of the tumor. RESULTS: Results, expressed as the slope of the binding curves and their leftward shift induced by diethylamine, showed different antibody populations between the two groups. Control sera showed a heterogeneous population of anti-BLG IgG antibodies, including antibodies of higher (steeper slope) and lower (more gradual slope) functional affinity. Cancer sera exhibited a less heterogeneous population of anti-BLG IgG antibodies, mostly with lower functional affinity. No change was observed in anti-BLG IgG antibody affinity in the 25 lung cancer patients tested 5 +/- 1 week after complete surgical excision of the tumor. CONCLUSIONS: These results document a persistent qualitative immunologic disturbance in patients with lung cancer, regardless of the type and extent of tumor. The potential relationship between this observation and the development of lung cancer, however, is presently unknown.
OBJECTIVE: To assess whether asymptomatic abnormalities, including thyroid auto-antibodies, were associated with an abnormal miscarriage rate or a poor obstetric outcome. DESIGN: Prospective study of thyroid auto-antibodies and thyroid function in an unselected obstetric population. SETTING: Saint-Pierrie Hospital, Brussels, Belgium. SUBJECTS: Seven hundred and thirty consecutive pregnant women attending the antenatal clinic. MAIN OUTCOME MEASURES: Miscarriage and pregnancy induced hypertension. RESULTS: Elevated antithyroperoxidase (TPO-Ab) and antithyroglobulin (TG-Ab) antibody titres are associated with an increased miscarriage rate. Also, asymptomatic thyroid abnormalities, mainly abnormal echo-structure but not antithyroid antibodies, are associated with pregnancy induced hypertension. CONCLUSION: The presence of thyroid auto-antibodies during pregnancy constitutes a marker of increased risk of miscarriage and poor obstetric prognosis.
Previous studies have suggested an inverse relationship between atopy and cancer of mucosal surfaces. Atopy is classically assessed by detecting specific immunoglobulin E (IgE) antibodies against inhalant allergens. However, Platts-Mills recently proposed that atopy is the ability of an organism to recognize and to respond to limited doses of allergens presented at the mucosal level by producing not only IgE, but also immunoglobulin A and immunoglobulin G (IgG) antibodies. The authors compared the prevalence of atopy in 103 patients with lung cancer (a model of mucosal cancer), 51 patients with chronic obstructive pulmonary disease matched for age, sex, and smoking habits with patients with lung cancer, and 102 healthy control subjects. The authors investigated whether the IgG response to antigens presented at the mucosal level, exacerbated in atopic subjects, might inversely be decreased in patients with lung cancer. Serum IgE antibodies against five common inhalant allergens (Dermatophagoides pteronyssinus [Der p1], Aspergillus fumigatus, grass pollen, and cat and dog danders) were detected through a radioallergosorbent test assay. Serum IgG antibodies against allergens naturally presented at the mucosal level (respiratory mucosa with Der p1 and digestive mucosa with betalactoglobulin [BLG] and soya proteins [SP]) were measured through a solid phase enzyme-linked immunosorbent assay test. Atopic status was assessed in 19 patients (18.4%) with lung cancer, 9 patients (17.6%) with chronic obstructive pulmonary disease (COPD), and 18 healthy control subjects (17.6%). Distributions of specific IgG levels were represented on frequency histograms after natural logarithmic transformation and showed reduced levels of anti-Der p1 and anti-BLG IgG in the cancer population compared with the control populations but similar levels of anti-SP IgG. Influence of sex, age, smoking habits, histologic type of cancer, and its extent could be excluded. The authors' results show no difference in the prevalence of atopy between the three groups. They document a selective, rather than general, defect in the immune response initiated at the mucosal level in patients with lung cancer, the most frequent mucosal cancer in man.
We describe here a simple, reliable and quantitative method to measure the alternative pathway (AP) dependent mode of complement activation for the lysis of rabbit erythrocytes. In the test the reciprocal of the plasma volume needed to destroy 50% of available rabbit erythrocytes is defined as the functional measure of this activity (AP50). The test was found to be highly reproducible both within and between assays with a coefficient of variation which was less than 5%. Sensitivity was also shown to be satisfactory and all of the plasma samples from the healthy blood donors which were tested could be assayed with precision. The specificity of the AP50 assay for AP complement activation was verified by the fact that a C4 affinity-depleted plasma gave an AP50 value within the normal range (52.8 U/ml) while a similar aliquot of the same plasma, affinity-depleted of factor B, gave an undetectable AP50 value (less than 10 U/ml). Furthermore, a sample was unable to lyse the target cells when heated to 50 degrees C or 56 degrees C, treatments which are known to destroy factor B and total haemolytic complement, respectively. To ensure inhibition of the classical pathway of activation. EGTA and MgCl2 were added during the assay. An advantage of this assay is that it is possible, using microplates, multipipettes and a spectrophotometer coupled to a computer, to semi-automate the procedure.
We report the case of a young man who developed severe asthma a few months after starting work in a factory producing a single type of mushroom: Pleurotus cornucopiae (a basidiomycete). Immunological investigations, performed with material recovered from the filtering devices of the mushroom's bed, led to demonstration of specific IgE and IgG against spore extracts and to isolation of one discriminant antigen (molecular weight: 10.5 kd). Current data concerning the underestimated role of the basidiomycetes in allergic asthma are reviewed.
Although the precise neuropathologic basis for eclamptic convulsions remains unclear, intracranial hemorrhage is frequently associated with fatal cases. Magnetic resonance imaging (MRI) is a recently developed neuroimaging technique that appears superior to other processes for defining intracranial anatomy and pathophysiology. This technique has not yet been reported in eclampsia. The authors performed serial MRIs on an eclamptic woman, with findings compatible with previously described neuropathologic changes.
Peripheral human blood lymphocytes from healthy blood donors were investigated in vitro to observe the influence of different doses of thymopentin on nonstimulated proliferation, candidin-stimulated proliferation, and phytohemagglutinin (PHA)-induced interleukin 2 (IL2) production. Concentrations of thymopentin ranging from 0.01 to 10,000 ng/ml were used. The proliferation response in non-stimulated cultures was significantly higher in the presence of 0.01, 1, 10, 1,000, and 10,000 ng/ml of thymopentin. There was no significant increase with 0.1 or 100 ng/ml of thymopentin. Thus, three separate peaks were present in these unstimulated cultures: at a concentration of 0.01 ng/ml; between 1 and 10 ng/ml, and between 1,000 and 10,000 ng/ml. These peaks possibly represent three different subpopulations with different sensitivities to different concentrations of thymopentin. Candidin-induced proliferation was significantly higher only at concentrations of 1 and 10 ng/ml of thymopentin, corresponding to the second peak in the unstimulated culture. No other thymopentin concentrations induced significant increase in the candidin-stimulated cultures. No IL2 production was observed in the unstimulated cultures, even in the presence of thymopentin. On the contrary, preincubation with different concentrations of thymopentin influenced PHA-induced IL2 production. A significant increase in the IL2 level was observed in the supernatant of the cultures if 1,000 ng/ml of thymopentin was used in the preculture period. This concentration corresponds to the third peak in the unstimulated cultures. No significant changes were observed with other concentrations of thymopentin. As the measured value of IL2 is a result of a balance between IL2 production and utilization, the above-mentioned findings need further investigation.(ABSTRACT TRUNCATED AT 250 WORDS)
Thymopentin, a synthetic pentapeptide corresponding to the active site of thymopoietin, has been shown to restore antibody production in old mice. A decrease in immune response can also be observed in elderly humans, which is mainly caused by defective T cell function. The present study shows that the immunomodulating properties of thymopentin involve both specific and nonspecific responses in a population of elderly people vaccinated with keyhole limpet hemocyanin (KLH) antigen. Furthermore, it is demonstrated that these effects depend upon the mode of administration of thymopentin: The specific KLH antibodies (IgM and IgG), measured by solid-phase radioimmunoassay, reach the highest titers after subcutaneous injection. The lowest titers are produced after intravenous injections, whereas the responses to placebo are between these two ranges. The nonspecific immunoglobulin production, measured by nephelometry, does not follow the same pattern, suggesting that different regulatory mechanisms are involved. Future implications of these findings are discussed.
Monoclonal antibodies were used to determine the level of circulating helper and suppressor T cells in 34 infants and adults with severe atopic dermatitis and in normal controls. The percentage of OKT3 (total T lymphocytes) was reduced significantly in all the atopic infants. The percentage of OKT8 (suppressor-cytotoxic T lymphocytes) was reduced significantly in all patients with active lesions. The percentage of T gamma lymphocytes was reduced in all the atopic patients with or without active lesions.
The effect of thymopentin administered i.v. or s.c. on the levels of circulating specific IgM and IgG KLH (key-hole limpet haemocyanine) antibodies and non-specific immunoglobulins were measured at weekly intervals in elderly volunteers for three subsequent weeks after vaccination with 500 micrograms KLH. As compared with the placebo group, specific IgM and IgG antibody responses significantly increased in the s.c. treated group, but remained at significantly lower levels in the i.v. treated groups. Increases in non-specific immunoglobulin levels were observed after vaccination in the placebo group; no such increases appeared in the groups treated with thymopentin. The results demonstrate the immunomodulatory effect of thymopentin in humans. It is assumed that, depending on the route of application (which indirectly represents different doses), thymopentin can either stimulate or inhibit immune processes. As an immunomodulator it may represent a new therapeutic tool for immunostimulation as well as for specific immunosuppression.
Monoclonal antibodies of the OKT series were used to identify total T lymphocytes (OKT3+) and their helper (OKT4+) and suppressor-cytotoxic (OKT8+) and suppressor-cytotoxic (OKT8+) subsets in 34 insulin-dependent diabetic children and in 39 young healthy controls. The diabetics have a moderate but significant reduction of the proportions of total T lymphocytes at the expense of the T helper subset; the proportion of suppressor-cytotoxic cells are normal. These abnormalities of the lymphocyte subpopulations are not related to the duration of diabetes, the control of the disease nor to the presence of autoimmune phenomena. The latter were found in 51.4% of patients.
Monoclonal antibodies of the OKT series were used to identify T lymphocytes (OKT3+) and their inducer (OKT4+) and suppressor-cytotoxic (OKT8+) subsets in the peripheral blood mononuclear cells (PBMC) of 32 healthy old-aged people more than 70 years old (16 men and 16 women) compared to 47 adults (29 men, 18 women) less than 40 years old. The absolute lymphocyte count in the peripheral blood was not significantly influenced by age or sex. Both the proportions and the absolute numbers of T3+ and T4+ cells were significantly lower in aged than in young participants. The proportions but not the absolute counts of OKT8+ cells were higher in the elderly. Most interesting is the influence of sex and these parameters. Old women have normal numbers and proportions of T3+, T4+ and T8+ cells when compared to young women. The latter have a significantly higher proportion of T8+ cells than young adult males. Old men have a striking reduction of both the numbers and proportions of OKT3+ and OKT4+ cells when compared with young men and with women. In addition, old men have an elevated proportion, but a normal absolute number, of OKT8+ cells. The responses of PBMC to phytohaemagglutinin extent (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) are reduced to the same extent in ageing male and female subjects when compared to young adults. In the older group, the magnitude of the lymphocyte response to PHA and Con A but not to PWM is negatively correlated with the proportions of OKT8+ cells. Surprisingly, these correlations are observed only in old women but not in old men. The latter finding excludes the possibility that the age-associated decline of the lymphocyte response to T cell mitogens is secondary to an imbalance between T4+ and T8+ lymphocytes.